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Experimental Diabetes Research
Volume 2012, Article ID 671673, 11 pages
Research Article

KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and Improves In Vitro Insulin Secretion and Viability

1Department of Pharmacology and Toxicology, University of Kansas, 5064 Malott Hall, Lawrence, KS 66045, USA
2Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, MS 2002, Kansas City, KS 66160, USA
3Department of Medicinal Chemistry, University of Kansas, Lawrence, KS 66045, USA

Received 3 August 2012; Revised 5 October 2012; Accepted 7 October 2012

Academic Editor: Mark A. Yorek

Copyright © 2012 Kevin Farmer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


KU-32 is a novel, novobiocin-based Hsp90 inhibitor that protects against neuronal glucotoxicity and reverses multiple clinical indices of diabetic peripheral neuropathy in a rodent model. However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on the in vitro viability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter the in vivo metabolic parameters of diabetic mice.